Theme 3 - 3a (antigens and antigen receptors) Flashcards
(89 cards)
1
Q
what is an immunogen
A
an antigen that promotes an immune repsonse in the body
2
Q
are all immunogens antigens
A
yes
3
Q
are all antigens immunogens
A
no eg self antigens don’t promote a response
4
Q
what is an antigen
A
any molecule that can bind to an antigen receptor
5
Q
what are the 2 types of antigen receptor
A
on surface of B cell
or
on surface of T cell
6
Q
what is the B cell antigen receptor called
A
IMMUNOGLOBULIN
either in the form of B cell receptor complex (on surface of B cell) or when they are SECRETED from the B cell (when the B cell become PLASMA CELLS) they are called ANTIBODIES
7
Q
what allows the immune system to respond rapidly to its SECOND encounter with a pathogen
A
its memory
8
Q
what triggers specific immune responses
A
antigens
9
Q
which cells are part of specific immunity
A
- APCs (antigen presenting cells)
- B and T lymphocytes w/ specific Ag receptors
10
Q
what are the main APCs
A
- monocytes
- dendritic cells
- macrophages
11
Q
what are the phases of an adaptiive immune response
A
1) RECOGNITION phase
2) ACTIVATION phase (antibody producing cell, effector T cells)
3) EFFECTOR phase (elimination of pathogen)
4) DECLINE (homeostasis)
5) MEMORY (surviving memory cells)
12
Q
where does most antigen recognition occur?
A
in secondary lymphoid tissues (eg lymph node)
13
Q
different antigens are detected how/where
A
they are detected in different secondary lymphoid tissues
- eg lymph node detects antigents from within tissue
- spleen detects antigens from blood
- mucosal tissues have other methods
14
Q
what is an antigen
A
Ag is any substance that binds to specific receptors on lymphocytes ie B cell receptor (BCR) or T cell receptor (TCR)
15
Q
what is an antigenic determinant/epitope
A
the part of the Ag that binds receptors
16
Q
what is an immunogen
A
any molecule or group of molecules that induce an immune response
17
Q
describe the relatioship between immunogens and antigens
A
ALL immunogens are antigens, NOT all antigens are immunogens
18
Q
what is a hapten
A
a small molecule that can ACT as an epitope but NOT elicit an immune response on their own, they have to be BOUND to something else to elicit an immune response
19
Q
an antigen can be what
A
- a protein/lipid/carbohydrate or a combination of these
- may be FOREIGN or ALTERED SELF molecule
- may be SOLUBLE or PARTICULATE, SIMPLE or COMPLEX with many different antigenic determinants each of which comprises a small number of AMINO ACIDS, CARBOHYDRATES or LIPID RESIDUES
20
Q
antigens are most commonly what
give examples
A
proteins or large polysaccharides from foreign organisms: eg components of bacterial cell walls, capsules, pili, flagella, proteins of viruses, fungi and protozoa
21
Q
non micorbe derived antigens can be what
A
- pollen
- food
- dust
- ‘self’ antigens from dead/senescent cells or altered self molecules
22
Q
how can antigens enter the body
A
- breaks in skin and mucous membranes
- direct injection (bite/needle)
- organ transplants/skin grafts
- M cells in the mucosal surfaces
23
Q
give examples of simple antigens
A
- benzene
- ovalbumin (from eggs)
- pollen
24
Q
give examples of complex antigens
what do they invoke
A
- Corona virus
- bacteria
these can have multiple epitopes, they invoke a POLYCLONAL immune response
25
give example of an exogenous antigen
- bacteria
26
are viruses endogenous or exogenous antigens?
viruses aren't 'living' until they are inside a host cell and can replicate
- the proteins that they express can end up on the SURFACE of the infected cell
- but since the cells are from the organism itself it is an ENDOGENOUS antigen
27
what type of antigen is a self antigen that cuases disease
an auto antigen
28
all antigens are not equally immunogenic, tru or false
true
29
what characteristics of an antigen give it HIGHER IMMUNOGENICITY
- larger
- INTERMEDIATE dose (high/low dose can cause lower immune response)
- entrance via SUBCUTANEOUS (skin)
- complex antigens
- in a PARTICULATE form and DENATURED
- have MULTIPLE differences to a self protein
- slow release ADJUVANTS, BACTERIA
- EFFECTIVE interaction with host MHC
30
how can we INCREASE the immunogenicity of an antigen used in vaccine
use of ADJUVANTS
31
what does an adjuvant do
| what are they freq used in
enhance the immune response to an antigen, making it MORE immunogenic
- freq used in vaccines
32
what do adjuvants inc
- persistence 'depot' (the antigen is present for longer before being cleared by liver)
- effective size (for uptake by APCs)
- activation of DENDRITIC CELLS, MACROPHAGES--> inflammatory cytokine production
33
what are examples of adjuvants
- COMPLETE FREUND'S ADJUVANT (oil, water, dead:lysed mycobacteria)
- alum (aluminium potassium sulphate)
34
which receptors are part of the adaptive (specific) immune system
BCR- B cell receptor (immunoglobulin/antibody)
| TCR- T cell receptor
35
which receptors are part of the innate (non specific) immune system
Pattern Recognition Receptors
36
which receptors are IN BETWEEN the innate and ADAPATIVE immune systems?
NK cells killer activatory immunoreceptors
| KARs such as NKG2D
37
what do B cell receptors bind
- bind 'native' antigen in solution/suspension
| - recognise the 3D conformation of the antigen via BCR (surface immunoglobulin or sIg)
38
what is BCR sometimes called
surface immunoglobulin (sIg)
39
what do T cell receptors bind
- binds linear arrays of approx 9 aa via TCR
| - antigen has to be processed and presented on an Ag presenting cell using MHC
40
what is the structure of antigen receptors
- includes IMMUNOGLOBULIN folds
- this consists of ANTI-PARALLEL BETA PLEATED SHEETS held together by disulphide bonds
- highly variable LOOPS on either side of B pleated sheet which give rise to functions
41
where are immunoglobulin folds found?
antigen receptors, adhesion molecules, MHC molecules
42
what are immunoglobulins
proteins that recognise and bind to a particular antigen with VERY HIGH SPECIFICITY
43
what are the 2 forms of immunoglobulins:
| the structure of the Ig or antibody molecule allows it to ?both recognise and bind
1) bound to the surface of B cells ---> BCR
2) made in response to exposure to the antigen ---> ANTIBODIES
- both molecules have the same structure but are either bound to the membrane or secreted by fully activated B cells (plasma cells)
- the structure of the Ig or antibody molecule allows it to both recognise and bind to antigen as well as carry out different effector mechanisms
44
what are the differences between BCR and antibody
- BCR has short SPACER segment which anchors it to the B cell
- BCR is in the TRANSMEMBRANE DOMAIN
other than this they are identical
45
the BCR and antibody made by one cell will do what
will recognise and BIND to ONE particular antigen with V HIGH SPECIFICITY
- will also be of the SAME CLASS of immunoglobulin (the constant regions of the antibodies will be same)
46
what are the names of the parts of immunoglobulin structure
1) MONOMER
2) AMINO TERMINAL seq of variability ) - Fab (frag Ag Binding)
3) REST OF MOLECULE (CONSTANT) -Fc
47
describe each part of immunoglobulin structure
1) MONOMER: flexible Y shaped molecule w/ 4 protein chains (2 identical light chains and 2 identical heavy chains)
2) AMINO TERMINAL has seq of VARIABILITY (V) has V heavy (VH) and VL (V light) which form ANTIGEN BINDING SITE - 'Fab' (fragment of antigen binding)
3) CONSTANT structure - Fc
- can be CL (constant light) which can be κ or λ chains
- or CH (constant heavy) which can be CH1, CH2, CH3, CH4 and stabilised by intrachain disulfide bonds
- Can be μ, γ, α, δ, or ε chains depending on the class
48
what happens in the variable region of immunoglobulin
it is the antigen binding site
49
what is the structure of the antigen binding site
- made up of Ig folds that contain 3 hypervariable loops between the strands of the β-pleated sheets
- called CDRs (complementarity-determining regions), which vary in length and amino acid composition
- this variability is what gives the immune system diversity, because each BCR is different
50
in which region of an immunoglobulin are effector functions ususally found
constant regions
| - these are mediated through binding to cellular Fc receptors and complement activation
51
what are the 5 classes of immunoglobulins
- IgM: found on surface of naïve B cells
- IgA, IgE and IgG – Found on the surface of B cells that have been activated and have undergone “class-switching”
- IgD – Found on all B cells (function unknown)
52
what determines the 5 classes of immunoglobulins
the genome of the B cell
| O the BCR and the ANTIBODY made by a certain B cell clone will be the SAME
53
different antibody types are induced by what
different types of antigen, the entry route of the antibody function needed to mould the immune response to the type of invader encountered
54
IgM has what shape
pentamer (5 copies of antibody join together)
55
```
IgA is found where
what is the class specific structural features of IgA
```
mucosal secretions
- it is a dimer, joined by the J chain and secretory component
56
what is the function of IgA
agglutination and neutralisation
57
what is the function of IgD
unknown
58
what is the function of IgE
triggers histamine release from basophils and mast cells
59
what is the function of IgG
Complement activation, agglutination, opsonization and neutralisation, crosses placenta to protect foetus
60
what is the function of IgM
Complement activation, agglutination and neutralisation
61
what does each B lymphocyte have in terms of immunoglobulin copies
has multiple copies of an immunoglobulin with single antigen specificity
- due to the ‘randomly’ generated antibody variable regions that occur genetically during B cell development
- but the BCRs on all an individuals B cells COMBINED can recognise millions of different antigenic determinants
62
since immunoglobulins dont have signalling molecules to signal to B cell that they have bound antigen what do they do
- using 2 Igα and 2 Igβ (CD79a and CD79b) and memb bound Ig (mIg)
- they have long cytoplasmic chains that have Immunoreceptor Tyrosine kinase Activatory Motif: ITAM
- when antigen binds variable region, you can get clustering of receptors which causes activation of ITAM
63
what happens once the ITAMs of Igα and Igβ transmit the signal if the mIgM binds antigen?
leads to development of either plasma or memory cells
- once developed into plasma cells they probably DONT express BCR on surface, instead they secret ANTIBODIES (same variable regions and Ig subclass as surface BCR)
- memory B cells cont to express BCR (but as IgG, IgA or IgE)
64
where do B cells develop from
progenitors in bone marrow
65
describe the process of B cell expression of BCR
genes coding heavy and light chains are rearranged giving each cell a unique BCR to recognise an epitope
- the resulting cells which cannot make functional heavy or light chains die by apoptosis (positive selection), as do those which bind to self molecules whilst arranging their BCRs (negative selection)
66
immunoglobulin genes contain which segments
segments known as VDJ segments:
- V = Variable Segments
- D = Diversity Segments
- J = Joining Segments
67
heavy and light chains cont which segments each
BOTH cont V and J
| HEAVY chain cont D segments
68
how is diversity achieved
there are many copies of each of these segments, one of these is selected each
69
antibodies recognise which part of an antigen
epitopes: the parts of antigen that contact the antigen binding sites of an antibody or T cell receptor
70
what must be the case for the antibody to fit
the molecular 'shape' of the epitope and the variable regions must 'fit'
71
epitopes can be what
linear or discontinuous
72
what is each antigen binding site made up of
the Complementarity Determining Regions (CDRs) of two different Immunoglobulin folds
- These are at the furthest extreme of the heavy (VH) and light chains (VL)
- These are so close together in the 3D structure of the antibody that they make one continuous paratope
73
what determines how tightly the epitope and paratope bind?
their complementarity
- the higher the complementarity the stronger the binding. The strength of the reaction is referred to as the affinity of the antibody
- generally: a high affinity antibody is more protective against pathogen than a low affinity antibody because it will bind antigens at lower concentrations
74
what is the antibody avidity
the total strength of binding of the Fab regions of the population of antibodies raised against an antigen, and involves the reaction with all antigenic determinants
75
which class of immunoglobulin has low affinity
IgM
76
describe affinity
ONE antigen binding site
| ONE epitope
77
describe avidity
MULTIPLE antigen binding sites
| REPEATED epitopes
78
IgM has high what and low what ?
LOW affinity
HIGH avidity: the 10 variable (Fab) regions, the have high avidity, and are still very effective against whole pathogens and are very effective activators of complement
79
what are the 2 main components of BCR
1) memb bound Ig
| 2) signalling chains CD79 alpha and beta
80
where are the parts of heavy chain of the memb bound Ig
- a short cytoplasmic domain
- a transmembrane region
- the rest of it is EXTRACELLULAR
81
what is the extracellular domain of the membrane bound HEAVY chains Ig on BCR composed of
- 4/5 Ig like domains
3/4 of these are CONSTANT regions
1 is a VARIABLE region
82
how are the two chains of the extracellular domain of memb bound Ig joined
disulphide bond in the HINGE region
83
what is the structure of the light chains on the extracellular domains of the memb bound Ig on BCR
two light chains are ATTACHED to the heavy chain (they dont go through the membrane)
- form TWO Ig like domains
84
on the memb bound Ig, where does the antigen bind
the TWO VARIABLE regions of the chains come together to form the antigen binding site
85
how many antigen epitopes can one memb bound Ig bind
TWO as there are TWO sets of variable regions
86
what does the memb bound Ig have to associate with to communicate to B cell that it has bound antigen?
CD79 alpha and beta
87
what is the structure of CD79 alpha and beta
- a small EXTRACELLULAR portion that has a Ig domain externally
- a transmembrane region
- a LONG CYTOPLASMIC tail that is able to SIGNAL (which have IMMUNORECEPTOR TYROSINE ACTIVATORY MOTIFS - ITAMS)
88
what does ITAM stand for
IMMUNORECEPTOR TYROSINE ACTIVATORY MOTIFS
89
what are the CD79 alpha chains joined by
BETA chains, which CO ASSOCIATE with MEMBRANE BOUND Ig to form BCR
- CD79 also has ITAMs
